Millions of surgeries are performed each year under local anesthesia and/or intravenous (IV) sedation in freestanding ambulatory surgery centers. In any procedure, the patient is often faced with significant distress and anxiety which can lead to many problems. In addition to the physiologic changes caused by anxiety and pre-procedural stress, the patient's ability to follow pre-op instructions is often compromised. This can be of a particular problem in patients such as diabetics who are often confused about which medicines and how much of each they should or should not take in the pre-op period. This, coupled with the fact that patients often need to refrain from eating or drinking (nothing by mouth or Latin: Nil Per Os or NPO) for an extended period of time prior to the procedure, can lead to problems such as significant and symptomatic hypoglycemic episodes.
Minor medical emergencies in a non-hospital, office-based environment can pose challenges. Often, in the stable and fully conscious patient with mild hypoglycemia, a glucose-rich Per Os (by mouth, Latin: Per Os or PO) drink is administered. Such intervention is practical in these mildly affected patients where a more acute intervention is not necessary.
In a more acute situation where quick reversal of hypoglycemia is required, dextrose may be administered via IV access. However, the option of IV administration would take some time to prepare and push even in the event that an IV is already in place. Intervention with IV dextrose alone would likely be slower than optimal or desirable in those patients who do not already have IV access.
Intervention in the form of the application of a sugar-rich substance such as cake icing to the buccal or sublingual mucosa is often advocated and a possible option in the event that an IV is not accessible or if dextrose infusion is not immediately available. This option, in addition to having no data supporting its efficacy, has other problems as well. Application should only be used in a fully conscious and alert patient due to the risk of pulmonary aspiration. There is also a dependence on patient compliance even in the conscious persons. If the sugar is swallowed, there would be a significant delay in the effects on blood glucose levels. Another problem is the delay necessary for the sugar, in the form of sucrose, to be broken down by sucrase in the oral cavity prior to being able to be transported transmucosally as glucose.
If the above treatments are not administered without delay, a patient, particularly those with brittle (labile) diabetes, may become comatose due to hypoglycemic brain injury. In certain situations this can lead to a persistent vegetative state without any expected neurologic improvement. Quick and acutely effective sources of glucose, administered expeditiously during crashing could be the difference between life and death. Of additional importance, the dose of dextrose required to effect a change in the blood glucose of an individual is approximately 5 to 15 grams—necessitating the ability to deliver a large dextrose payload.
The problem and risk of hypoglycemic episodes for the diabetic is not limited to the medical or dental office, however, and constant access to a source of rescue glucose is crucial. It is not uncommon for physicians to recommend that these individuals keep a tube of cake icing or other glucose rich substance on their person for quick application in such events. As enumerated earlier, the use of either cake icing or PO forms of rescue glucose pose significant problems and are suboptimal for these same reasons.
Hypoglycemia of the newborn and hypoglycemia associated with severe systemic illness is a significant health problem worldwide, particularly in the undeveloped world. Hypoglycemia can be closely linked to a significant proportion of the two hundred and twenty-five thousand (225,000) yearly malarial deaths in African children under the age of five (5) years. The preferred treatment in most cases is correction via IV dextrose infusions. Problems with this treatment are plentiful in the undeveloped areas that are poor both in terms of monetary and human capital. Delay to infusion can be caused by many reasons. Most health care facilities do not have the supplies. Families of the sick are given prescriptions for needed supplies/medications and they must go and find not only the money to buy these supplies but a pharmacy that has the supplies available prior to returning to the hospital for initiation of treatment. Additionally, it can be hard to obtain IV access in a small, acutely ill (dehydration, shock, unconscious) child. IV access carries other risks, including pain, risk of blood-borne pathogen transmission, and possible local or systemic infection associated with venous catheterization.
The correction of hypoglycemia by placing a spoon full of granulated table sugar (sucrose) under the tongue has been studied in this population by the medical community and the results were promising when compared to IV dextrose infusion. Problems with this very basic method, however, included early swallowing of the loose, granulated sugar by the children which resulted in treatment failure. Additionally, table sugar is sucrose and must be broken down to glucose and fructose by sucrase in the oral cavity prior to transport transmucosally.
Hypoglycemia is of immediate concern in the person found by healthcare workers to be unconscious due to an unknown cause. Classically, such a patient is always treated, immediately on arrival in the emergency department, with an intravenous administration of a three drug combination including dextrose, thiamine, and naloxone. The decision to administer these drugs is a reflexive decision (i.e. all unconscious patients with a significantly and abnormally depressed mental status, without a clear or known cause for such, are reflexively administered this “coma cocktail.”) If such a transmucosal dosage-form were possible, under the reflexive direction of a proper protocol, it would allow for the administration of the classic cocktail constituents by emergency medical services providers immediately upon arrival to the scene and long before IV access or reaching the hospital emergency department.
Long-distance athletes have a need to obtain hydration, electrolytes, and carbohydrates during the episodes of intense and prolonged exertion that they often put themselves through. Many different carbohydrate formulations, predominantly meant to be consumed orally, have been developed to target this population. A popular embodiment involves a gel-type formulation that is stored in a small pouch and meant to be consumed at some time period during the extended physical exertion. Targeting the PO route with these carbohydrate loads have multiple unwanted side effects—all of which have to do with the normal gastrointestinal physiology. Stimulation of the gastrointestinal tract with a load of carbohydrate, causes increased neuronal activity to the area leading to increased peristalsis which combined with the decreased blood supply to the bowels during strenuous exertion produces the common sensation of gastrointestinal uneasiness or queasiness after consuming the product. The next step in physiology is an increased shunting of blood away from the muscles needing this perfusion to the splachnic circulation towards the bowels. Athletes also describe the subjective feeling of a vague central heaviness.
Prior art, with regard to oral, transmucosal drug delivery does not describe a method by which large payloads of active pharmaceutical agent, on the order of grams, can be delivered systemically. The prior art of dosage form fabrication for oral transmucosal drug delivery describes gels, tabs, patches, sprays. It lacks in having not described a form by which large payloads (on the order of multiple grams) can be delivered systemically through the mucosa of the oral cavity. It has also not described anatomic delivery forms for oral application.